This invention is generally related to a non-invasive blood glucose monitor, and more particularly to a non-invasive blood glucose monitor based on micro-optical-mechanical-electro-system (MOMES).
Non-invasive measurement of blood glucose concentration offers many advantages over invasive measurements, since the intermittent tests, which are widely practiced by diabetic patients, involve pain and discomfort from frequent finger-pricking.
Non-invasive measurement approaches of blood glucose concentration based on absorption measurements in the infrared region have been explored more than 20 years.
An early U.S. Pat. No. 4,169,676 (October, 1979) to Kaiser shows a method for the use of attenuated total reflection glucose measurement by placing the attenuated total reflection plate directly against the skin and especially against the tongue. The procedure and device shown there uses a laser and determines the content of glucose in a specific living tissue sample by comparing the infrared absorption of the measured material against the absorption of infrared in a control solution by use of a reference prism.
Another early U.S. Pat. No. 4,655,225 (April, 1987) to Dahne, et al. describes an apparatus for non-invasively measuring the level of glucose in a blood stream or tissues. The method is photometric and uses light in the near-infrared region. Dahner""s device is jointly made up to two main sections, a light source and a detector section. They may be situated about a body part such as a finger. The desired near-infrared light is achieved by use of filters. The detector section is made up of a light-collecting integrating sphere or half-sphere leading to a means for detecting wavelengths in the near-infrared region.
In recent years more methods and apparatus have been proposed. U.S. Pat. No. 5,974,337 (Oct. 26, 1999) describes an instrument for non-invasive glucose measurement. The described instrument irradiates the distal phalanx of a subject""s finger with light in the near infrared. The transmitted or reflected radiation is detected and analyzed and an estimate of blood glucose level made. The signal is coupled with a fiber optic probe by means of a conventional arrangement of lenses and mirrors. Illumination fibers and collection fibers are provided in separate structures.
U.S. Pat. No. 5,424,545 (Jun. 13, 1995) describes an instrument for non-invasive blood analyte determination that relies on calorimetric analysis to arrive at a blood analyte determination. A light beam is coupled with an illumination fiber by means of lenses and mirrors.
U.S. Pat. No. 6,064,898 (May 16, 2000) describes a non-invasive blood component analyzer that provides built-in path length monitoring to allow use in subjects of varying finger size. It provides a light source either from LED""s or from a lamp. The light is simply emitted in the vicinity of the sampling site and coupled through the atmosphere.
U.S. Pat. No. 5,782,755 (Jul. 21, 1998) discloses a method of spatial resolved diffused reflectance for measurement of glucose in a biological system. It uses multiple spot sources, such as flash bulbs, and a single detector. The light sources are spaced different distances along a single line from a detector and are sequenced at different time intervals to derive the spatial reflectance profiles.
All above-mentioned methods and apparatus are impossible to detect on the spectrum the relative heights of the waveform (peak and trough), which are finely varied by the coupling of glucose and protein, resulting in insufficiency in the accuracy and reproducibility of the blood glucose measurement.
U.S. Pat. No. 6,031,233 (Feb. 29, 2000) describes an apparatus based on an infrared spectrometer. Light is emitted from a lamp and passed through an acousto-optical tuning filter for wavelength selection. The acoustic-optical tuning filter is composed of a high frequency electric power source, a high frequency vibrator, and an acousto-optic variable oscillator. The filtered light is focused through one or more lenses and directed toward the measurement site through a window. The use of the acousto-optical tuning filter for wavelength selection requires a wavelength synthesizer and an RF amplifier.
This apparatus is not only complicated and expensive but also leaves several problems to be solved.
Problem 1, the light absorbed by the tissue subjected to analysis constitutes, together with other losses due to scattered stray radiations and RF interference, signals inherent to the practice of the method and the apparatus components, the background response noise from which the useful signals must be separated.
Problem 2, skin tissue is composed of various compositions of fat and protein, as well as veins, arteries, and bones. Such heterogeneous structure can contribute to local variation of the light absorption and scattering.
Problem 3, a temporal variation in glucose concentration is associated with blood flow changes during a heartbeat process of the blood subject of measurement. Data received at individual points of the heartbeat process are not the same.
Problem 4, portable and handheld non-invasive blood glucose instruments are demanded for point of care and in home use. Such instruments in which light is coupled by means of an arrangement of conventional lenses and mirrors have high space requirements and they are highly vulnerable to mechanical shock.
Accordingly, it is intended to provide a non-invasive blood glucose monitor of solving the aforementioned problems, excelling in accuracy and reproducibility.
It is an object of the present invention to provide a non-invasive blood glucose monitor with main components being MOMES devices so that it is small enough to fit the palm of your hand.
Furthermore, it is an object of the present invention to provide a non-invasive blood glucose monitor that enables to use a combination of modulated monochromatic infrared light and synchronous detection technology for maximizing the electronic single-to-noise ratio.
It is yet another object of the present invention to provide a non-invasive blood glucose monitor that enables the use of a tunable filter to eliminate stray infrared radiation so that the optical signal to noise ratio can be maximized.
It is yet another object of the present invention to provide a non-invasive blood glucose monitor that enables selecting and switching of the illumination infrared light in an infrared wavelength range so that an infrared absorbance spectrum of the blood subject of measurement can be obtained.
It is yet another object of the present invention to provide a non-invasive blood glucose monitor that enables scanning over a large area of measurement so that the poor reproducibility caused by non-homogeneity of the subject of measurement can be overcome.
It is yet another object of the present invention to provide a non-invasive blood glucose monitor that enables the measurement of blood glucose in a period of a heartbeat and an average can be made to eliminate the blood flow changes due to heartbeat.
In order to realize the above-mentioned objects, the present invention provides a MOMES-based non-invasive blood glucose monitor consisting primarily of a micromachined infrared interferometer array, a micromachined infrared mechanical modulator array, a micromachined infrared tunable filter, and needed driver and signal processing integrated circuits.
The micromachined infrared interferometer array, micromachined infrared mechanical modulator array, and micromachined infrared tunable filter are an adaptation of Fabry-Perot devices that employ the principle of optic interference. The basic unit is a Fabry-Perot cavity consisting of two parallel planar reflectors separated by an air gap. At least two flexible beams support one of the two reflectors. Applying a voltage to the two reflectors can change the length of the air gap.
Infrared light passes through one of the two reflectors and is multiply reflected within the cavity. The multiply transmitted light beams interact with each other creating optical interference effects, which result in the transmission, through the other reflector, of only one particular wavelength and its harmonics.
The MOMES is a device that is, in general, built using micromaching and standard integrated circuit techniques. Starting with a silicon wafer and depositing a series of films such as nitrides, polysilicon, oxides and metals, one builds a complex three-dimensional structure in much the same way one builds an integrated circuit. However, unlike integrated circuits, one then releases the device by etching away the oxides, producing a structure that can move. This subtle change in processing allows one to produce optical devices that move, including data modulators, variable attenuators, optical switches, active equalizers, add/drop multiplexers, optical cross-connects, dispersion compensators, all-optical switches, filters, tunable laser sources, active packages and adaptive optical elements.
The micromachined infrared interferometer array and micromachined infrared detector are mounted on the surface of a substrate and the micromachined infrared mechanical modulator array and micromachined infrared tunable filter are mounted on the surface of another substrate. The substrates may incorporate three driver circuits and a photo-integrated circuit. The monitor further consists of at least one infrared thermal radiator, at least one collimator, a band pass infrared filter, an electronic filter, an A/D converter, a microprocessor, and a display.
In operation of the monitor, an infrared light source irradiates an infrared light. The infrared light passes through a band pass filter that covers a wavelength range within 0.8 to 2.5 xcexcm or 2.5 to 25 xcexcm. An actuated micromachined interferometer divides a monochromatic infrared light from the filtered infrared light. An actuated mechanical modulator converts the monochromatic infrared light into an alternating monochromatic infrared light. The alternating infrared light illuminates a first portion of a blood subject of measurement. A back-diffused alternating infrared light from the first portion of the blood subject of measurement passes through the actuated micromachined tunable filter. The infrared detector converts the filtered back-diffused alternating infrared light into an alternating electronic signal. After amplification the alternating electronic signal is demodulated and converted into a digital signal. A microprocessor is used to process the digital signal for producing the data of the first portion of the blood subject. In the same way the rest of the micromachined interferometers and mechanical modulators are actuated in turn for producing the blood glucose data of the other portions of the blood subject. Again in the same way a plurality of monochromatic infrared lights each with a central wavelength are divided from the infrared light and each monochromatic infrared light is used to repeat the above-mentioned steps for collecting a corresponding blood glucose data of the blood subject.
The foregoing monitor offers a number of advantages. Since the monitor is based on MOMES, it can be made small enough to fit into the palm of your hand. It allows using mature microelectronic technology for batch-production so that the production cost can be reduced substantially. It permits the infrared light being passively aligned where the optics structure of the monitor can be expected to be compact and reliable. It allows using synchronous detection so that high electronic signal to noise ratio can be obtained. Its tunable filter can eliminate stray infrared so that the optical signal to noise ratio can be maximized. In addition, it allows averaging of back-diffused infrared light over a large area of the blood subject. Such averaging reduces any non-homogeneity of the illumination structure in the tissue and thus improves reproducibility and reliability of the measurements.